Journal of Molecular Medicine

, Volume 81, Issue 8, pp 455–470 | Cite as

Inflammatory mediators and islet β-cell failure: a link between type 1 and type 2 diabetes

  • Marc Y. DonathEmail author
  • Joachim Størling
  • Kathrin Maedler
  • Thomas Mandrup-Poulsen
Invited Review


Pancreatic islet β-cell death occurs in type 1 and 2 diabetes mellitus, leading to absolute or relative insulin deficiency. β-cell death in type 1 diabetes is due predominantly to autoimmunity. In type 2 diabetes β-cell death occurs as the combined consequence of increased circulating glucose and saturated fatty acids together with adipocyte secreted factors and chronic activation of the innate immune system. In both diabetes types intra-islet inflammatory mediators seem to trigger a final common pathway leading to β-cell apoptosis. Therefore anti-inflammatory therapeutic approaches designed to block β-cell apoptosis could be a significant new development in type 1 and 2 diabetes.


Apoptosis Interleukin 1 Mitogen-activated protein kinase Jun N-terminal kinase Extracellular signal-regulated kinase 



Death domain


Evolutionary conserved signaling intermediate in Toll/IL-1 pathways


Endoplasmic reticulum


Extracellular signal-regulated kinase


Fas-associated death domain


Fas ligand


Free fatty acid


Fas-associated death domain-like IL-1β converting enzyme inhibitory protein




IκB kinase




IL-1 type 1 receptor


IL-1 receptor antagonist


Inducible nitric oxide synthase


IL-1R activated kinase


Interferon regulatory factor


Inhibitory κB protein


Janus tyrosine kinases


c-jun N-terminal kinase


Mitogen-activated protein


Mitogen-activated protein kinase


MAPK/ERK kinase kinase


Mediator of receptor induced toxicity


Nuclear transcription factor


Nonobese diabetic


Pancreatic duodenal homeobox factor


Protein kinase C


Reactive oxygen species


Stress-activated protein kinases


Sarco-/endoplasmic reticulum Ca2+ ATPase


Signal transducer and activator of transcription


Transforming growth factor β-activated kinase


Tumor necrosis factor


TNF receptor associated death domain


TNF receptor associated factor



This work was supported in part by the Juvenile Diabetes Research Foundation International Grant # 4-2002-457, the Danish Diabetes Association and Novo Nordisk (J.S., T.M.P.) and by the Swiss National Science Foundation Grants #3200-067049.01 and PP00B-68874/1 and by the Max Cloetta Foundation (M.Y.D.).


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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Marc Y. Donath
    • 1
    Email author
  • Joachim Størling
    • 2
  • Kathrin Maedler
    • 1
  • Thomas Mandrup-Poulsen
    • 2
    • 3
  1. 1.Division of Endocrinology and DiabetesUniversity HospitalZurichSwitzerland
  2. 2.Steno Diabetes CenterGentofteDenmark
  3. 3.Department of Molecular Medicine, Rolf Luft Center for Diabetes ResearchKarolinska InstituteStockholmSweden

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